Efficacy of immunomodulatory therapy with interferon-β or glatiramer acetate on multiple sclerosis-associated uveitis | Archivos de la Sociedad Española de Oftalmología (English Edition)

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Optic neuritis is the most frequent ocular expression of MS, with an incidence approaching 30% of these patients.<a class="elsevierStyleCrossRef" href="#bib0115">2</a> Foveal inflammation is significantly less frequent.It has been demonstrated that patients with MS exhibit higher risk of developing uveitis, probably due to sharing target antigens, genetic susceptibilities or alterations in immunological homeostasis.<a class="elsevierStyleCrossRefs" href="#bib0115">2,3</a> Approximately 1% of patients with MS develop uveitis episodes in the course of the disease, and 1% of patients with uveitis associate MS.<a class="elsevierStyleCrossRef" href="#bib0125">4</a> This association between uveitis and MS indicates that both entities share etiopathogenic mechanisms and therefore both could respond to the same treatment.Uveitis episodes usually respond to locally or systemically administrated corticoids. Interferon-β (IFNβ) or glatiramer acetate are immunomodulator agents that efficiently diminish the frequency and severity of MS episodes as well as the progression of the disease.<a class="elsevierStyleCrossRefs" href="#bib0125">4–9</a> In addition, treating uveitis episodes associated to MS with IFNβ seems to have a beneficial effect as regards visual acuity and intraocular inflammation.<a class="elsevierStyleCrossRef" href="#bib0155">10</a> To date, there is no clear evidence about the efficacy of any medication capable of reducing the number of uveitis episodes in patients with MS.The main objective of the present study is to analyze the role of immunomodulator therapy with IFNβ or glatiramer acetate in the reduction of the number of intraocular inflammation episodes in patients with uveitis associated to MS.Material and methodsA retrospective, non-controlled study of patients with uveitis and MS diagnostic that received immunomodulator treatment included in the database of the Ophthalmology and Neuroimmunology Dept. of the Vall d’Hebron hospital of Barcelona between 1990 and 2013. The study was approved by the ethics committee of the authors’ institution in accordance with the guidelines of the Helsinki declaration and good clinical practices. All patients read and signed an informed consent document, authorizing the use of the information in their medical records for the present study.The MS diagnostic was established by the specialist of the Neuroimmunology Dept. on the basis of a neurologic examination and magnetic resonance findings, in accordance with the revised McDonald criteria.<a class="elsevierStyleCrossRef" href="#bib0160">11</a>The study included patients with a definitive MS diagnostic and were treated with IFNβ or glatiramer acetate prescribed by the specialist of the Neuroimmunology Dept. for controlling the course of MS and who also exhibited clinically significant intraocular inflammation episodes. In addition, all the patients were examined by an internist physician and carried out the appropriate diagnostic studies to discard the possibility of other related systemic diseases. The study excluded the patients with self immune diseases that could be related to uveitis, patients with less than 12 months follow-up or with incomplete clinical records.The classification of uveitis was based on the criteria of the International Uveitis Study Group (IUSG)<a class="elsevierStyleCrossRef" href="#bib0165">12</a> as regards the anatomic location (anterior, intermediate, posterior or panuveitis). A new outbreak of intraocular inflammatory activity was regarded as an increase in 2 or more cellularity levels in the anterior chamber or vitreous cavity, applying the criteria of the SUN Working Group,<a class="elsevierStyleCrossRef" href="#bib0170">13</a> associated to diminished vision or increased myodesopsia.The anterior uveitis episodes were treated with topical corticoids (dexamethasone 1mg/ml, eyedrops) and midriatics (1% cyclopentolate eyedrops).The intermediate and posterior uveitis episodes were treated with systemic corticoids (1mg/kg prednisone) in cases exhibiting bilateral involvement, or with subtenon or intraocular corticoid injections (1mg/ml triamcinolone acetonid) in cases with unilateral involvement or cystic macular edema.Sector photocoagulation with argon laser was applied in occlusive vasculitis with marked retinal ischemia evidenced in fluorescein angiography.All patients received immunomodulator treatment (IFNβ or glatiramer acetate) prescribed for controlling MS by Neuroimmunology Dept. specialists. Immunomodulator treatment was not prescribed in any case for controlling uveitis episodes. Patients treated with IFNβ1a were given a weekly intramuscular dose of 30μg (Avonex®, Biogen Inc., Cambridge, Massachusetts, USA). Patients treated with glatiramer acetate were given daily subcutaneous 20mg injections. The type of medication was based on the criteria of neurologists for controlling the course of MS. The degree of disability associated to MS was assessed according to the Expanded Disability Status Score (EDSS).<a class="elsevierStyleCrossRef" href="#bib0175">14</a>The statistical analysis was developed with the SPSS for Windows, version 17.0 (SPSS, Chicago, IL, USA). The Wilcoxon test for paired data was applied for comparing the number of uveitis episodes exhibited by patients during the immunomodulator treatment vs without immunomodulator treatment. Taking into account that the follow-up period is different before vs during immunomodulator treatment, the measurement scale was unified in order to make said periods comparable: calculating the mean number of uveitis episodes/years of follow-up (before and during the immunomodulator treatment). A value of p<0.05 was taken as statistically significant.ResultsOverall, 16 patients with uveitis episodes associated to MS in treatment with immunomodulator medicaments were initially included in the study. However, 3 were excluded (2 patients with less than 12 months follow-up and one due to incomplete medical records). Taking into account the above inclusion and exclusion criteria, the results of 13 patients (7 females and 6 males) were analyzed after a mean follow-up of 148.61±84.30 months (range, 12–252 months).Mean age at uveitis episodes diagnostic was 39.7±9.5 years (range, 21–57 years); and presentation of neurological symptoms of 35.3±8.5 years (range, 21–49 years).Neurological symptoms preceded uveitis in 9 of the 13 patients (69.2%) with a mean time period of 114 months (range, 32–216 months); whereas in the remaining 4 patients uveitis appeared before neurological symptoms in a mean time period of 86 months (range, 20–216 months).Uveitis episodes were bilateral in 10 of 13 patients (77%). Patients had a mean of 4.15 intraocular inflammation episodes (range, 1–10 episodes) throughout the follow-up period. In 11 patients (84.6%) the predominant clinic form was intermediate uveitis, with 6 associating significant anterior inflammation. Three patients exhibited occlusive retinal vasculitis and a further case had posterior uveitis. This unique case was classified as a multifocal posterior retinochoroiditis. Ocular fundus examination revealed multiple cream-colored retinochoroidal lesions in the posterior pole of both eyes, with exudation in the early and intermediate phase of fluorescein angiography. A range of analytical and imaging tests (thorax x-ray and CAT) were made on this patient to discard a sarcoidosis diagnostic. In this unique patient, MS had been diagnosed 18 years prior to the onset of retinochoroidal lesions and exhibited a secondarily progressive form of MS.Medical treatment for controlling intraocular inflammation required oral prednisone for all patients. It became necessary to associate an immunosuppressant (cyclosporine) for 2 patients who were not taking immunomodulatory treatment at the time. When subsequently said patients initiated treatment with immunomodulator medicaments for controlling the course of MS, the intraocular inflammation episodes resolved without having to utilize cyclosporine. In 5 eyes of 3 patients, the presence of cystic macular edema was identified and treated with periocular triamcinolone injections.Occlusive vasculitis episodes were detected in 4 eyes of 3 patients (23%), who developed neovascularization in the retina and one in the optic disk. They were all successfully treated with sector argon laser photocoagulation of the compromised area. None of the patients developed iris neovascularization or neovascular glaucoma.Clinic characteristics of multiple sclerosisThe course of MS was recurrent-remitting in 11 patients (88.9%) and secondarily progressive in 2 patients (11.1%). Only one patient exhibited a secondarily progressive form of MS when uveitis was diagnosed. The clinic characteristics of the 13 patients are shown in detail in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The mean disability value as per EDSS at the last visit was globally 3.8 for the series. The patients who exhibited neurological symptoms prior to uveitis had a higher mean EDSS score in the last visit (mean 4.53; mean follow-up, 176.6 months) compared to those who exhibited uveitis prior to neurological symptoms (mean 2.62; mean follow-up, 120 months), although the difference was not statistically significant (U Mann–Whitney test, p=0.306).Ten patients received immunomodulator treatment with IFNβ (mean treatment duration: 41.5 months) and 3 patients were treated with glatiramer acetate (mean treatment duration: 11.3 months), according to the criteria of neuroimmunology specialists for controlling the evolution of MS. None of the patients exhibited active uveitis when beginning immunomodulator therapy.A statistically significant reduction of the mean number of uveitis episodes/follow-up years during treatment with immunomodulator medicaments (IFNβ or glatiramer acetate) was evidenced. The achieved reduction was 0.36 uveitis episodes/year, compared to the period of time during which patients did not receive immunomodulator treatment (Wilcoxon test for paired data, p=0.02). <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows a detailed description of immunomodulator therapy and uveitis episodes.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>ComplicationsSix out of 13 patients (46%) in treatment with immunomodulator therapy exhibited side effects related to IFNβ or glatiramer acetate, consisting in flu-like symptoms in 3 patients (23%) and skin rash in 3 patients (23%) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Immunomodulator treatment was not discontinued in any case, following the criteria of the Neuroimmunology Dept. specialists.DiscussionThe present study collected the data of 13 patients with a confirmed diagnostic of MS and intraocular inflammation episodes. Even though several studies described said association, there are few series with higher amounts of patients published in the literature.<a class="elsevierStyleCrossRefs" href="#bib0115">2,10</a> Demographic and chronological data of the series match those of other published series<a class="elsevierStyleCrossRefs" href="#bib0150">9,11</a> with the association between MS and uveitis being characteristic in young females with recurring-remitting forms of MS. The predominance of the females in this association varies between 60%<a class="elsevierStyleCrossRef" href="#bib0115">2</a> and 82%<a class="elsevierStyleCrossRef" href="#bib0180">15</a> in different series.In some studies, the appearance of neurological symptoms can precede intraocular inflammation (up to 60% of cases in some series<a class="elsevierStyleCrossRef" href="#bib0165">12</a>), whereas in other studies uveitis episodes preceded neurological symptoms up to several years.<a class="elsevierStyleCrossRef" href="#bib0185">16</a> Even though the majority of patients in the present series had MS diagnosed when uveitis expressed, 4 patients (30.7%) first had intraocular inflammation episodes, with a considerable time interval before the onset of neurological symptoms.A recently published study<a class="elsevierStyleCrossRef" href="#bib0190">17</a> indicates that the concomitant presence of uveitis in patients with MS could be a positive prognostic factor for the severity of MS. In accordance with said study, the majority of the present study patients developed recurring-remitting forms of MS. In contrast with other published series,<a class="elsevierStyleCrossRefs" href="#bib0155">10,16,18</a> the patients of this series who had uveitis before neurological symptoms demonstrated better prognosis in what concerns final neurological disability measured in the EDSS scale when compared to those whose neurological symptoms expressed before uveitis, although this difference was not statistically significant and could be attributed to the limited number of patients included in the series. These findings should be confirmed in future studies with higher numbers of cases.The effectiveness of IFNβ in patients with MS<a class="elsevierStyleCrossRefs" href="#bib0125">4,5</a> and/or optic neuritis has been demonstrated.<a class="elsevierStyleCrossRef" href="#bib0125">4</a> Jacobs et al.<a class="elsevierStyleCrossRef" href="#bib0135">6</a> demonstrated that beginning treatment with IFN at the first demyelinizing event such as optic neuritis is beneficial for patients with cerebral lesions shown in magnetic resonance that indicate a high risk of clinically definitive MS. The efficacy of this therapy has been confirmed in subsequent clinic trials.<a class="elsevierStyleCrossRefs" href="#bib0140">7,8</a>In the experimental allergic encephalomyelitis animal model, a classic MS model in experimentation animals, it was demonstrated that animals could also develop bilateral uveitis episodes,<a class="elsevierStyleCrossRef" href="#bib0200">19</a> and that treatment with IFNβ1 diminished intraocular inflammation.<a class="elsevierStyleCrossRef" href="#bib0205">20</a>In clinic trials, glatiramer acetate has demonstrated its efficacy in patients with recurring-remitting forms of MS diminishing recurrence rates and demyelinizing activity assisted by magnetic resonance.<a class="elsevierStyleCrossRef" href="#bib0165">12</a>There are no previous studies assessing the effect of immunomodulator therapy (IFNβ or glatiramer acetate) in what concerns the number of intraocular inflammation episodes in uveitis associated to MS. Becker et al.<a class="elsevierStyleCrossRef" href="#bib0155">10</a> demonstrated a beneficial effect of IFN in 13 patients with uveitis associated to MS, in terms of visual acuity improvement and intraocular inflammation activity. However they did not to research whether said therapy could diminish the number of uveitis episodes. The authors have not found other series in the literature referring to the effect of glatiramer acetate in uveitis associated to MS, the present paper being the first in this regard.The results of the present study demonstrate a statistically significant reduction in the number of intraocular inflammation episodes in patients being treated with IFNβ or glatiramer acetate, compared to the same patients before immunomodulator treatment. This seems to indicate the existence of shared antigen factors between neurological and ophthalmological expressions of the uveitis-MS range with similar pathogenic mechanisms. This beneficial effect could be particularly interesting for patients with partial resistance to systemic corticoids or immunosuppressant medicaments. The majority of patients did not exhibit relevant side effects attributed to immunomodulator therapy and those which did appear were well tolerated in the majority of cases.Intermediate uveitis was the most common expression in the present series, in accordance with the findings of the majority of uveitis and MS series.<a class="elsevierStyleCrossRefs" href="#bib0170">13–15</a> However, in other studies the posterior or anterior uveitis forms appear with greater frequency.<a class="elsevierStyleCrossRefs" href="#bib0115">2,16</a> These differences could be partly due to the different interpretation of the IUSG uveitis classification criteria<a class="elsevierStyleCrossRef" href="#bib0165">12</a> because, even though intraocular inflammation predominates at the pars plana level in the majority of cases, it could sometimes extend toward the iris and the anterior chamber.<a class="elsevierStyleCrossRef" href="#bib0175">14</a>The results of the present study demonstrate that corticoid therapy enables adequate control of intraocular inflammation episodes associated to MS in the majority of cases, requiring immunosuppressant agents only in isolated cases resistant to corticoid treatment (only 2 in the present series). Immunomodulator therapy was not prescribed in any case for controlling uveitis episodes, as the intraocular inflammation outbreaks were adequately controlled with corticoid therapy. Accordingly, it was not possible to assess the effect of immunomodulator therapy on the inflammatory activity in the anterior chamber, vitreous cavity, macular edema or retinal vasculitis. Due to the small sample size it was not possible to carry out the comparative study of the efficacy of treatment with IFNβ against glatiramer acetate in the reduction of uveitis episodes. Taking into account the findings of Becker et al.,<a class="elsevierStyleCrossRef" href="#bib0155">10</a> treatment with IFNβ should be considered in unique uveitis cases that are resistant to corticoid therapy. In their study, Becker et al. treated 13 patients with uveitis and MS refractory to steroid treatment with IFN, obtaining visual acuity improvements in 71% of patients and avoiding the use of steroid therapy in 69 of patients after 2 years of treatment with IFN.<a class="elsevierStyleCrossRef" href="#bib0155">10</a> However, it is also necessary to consider the recent study by Jouve et al.<a class="elsevierStyleCrossRef" href="#bib0210">21</a> that shows that the use of IFN for controlling MS in patients with concomitant uveitis could be associated to poor evolution of uveitis. In said study, patients with uveitis and MS treated with IFN developed higher percentages of chronic uveitis.<a class="elsevierStyleCrossRef" href="#bib0210">21</a> The limited number of patients in both studies, as well as its retrospective nature, do not enable definitive conclusions about the matter. Additional prospective studies are necessary with higher numbers of patients to obtain further evidence about the efficacy of treating patients with uveitis associated to MS with IFN.The limitations of the present study include its retrospective design, the limited number of cases and the fact that spontaneous inflammatory activity improvements might not have been recognized. Considering that MS can exhibit a recurring-remitting course and that uveitis can sometimes follow the pattern of the underlying MS, patients might have improved regardless of the treatment they were receiving. In addition, caution is advised when interpreting the present results because, by studying a limited number of cases and a different follow-up period before and during immunomodulator treatment, small changes in the number of intraocular inflammation episodes could have repercussions for statistical significance. For this reason, even though this study found a statistically significant reduction in the mean of uveitis episodes per follow-up year during immunomodulator treatment, this finding has only exploratory value and should be confirmed by series with higher numbers of cases and longer follow-up periods. The present series has studied the effect of immunomodulatory treatments on the number of uveitis episodes associated to MS. The design of the study does not allow an assessment of the effects of immunomodulator therapy on inflammatory activity in the anterior chamber, vitreous cavity, macular edema or retinal vasculitis. It would be of interest to carry out a prospective study with more patients to assess the efficacy of immunomodulatory treatments on intraocular inflammatory activity as well as to compare the differences or similarities between both immunomodulator treatments.In conclusion, treatment with IFNβ or glatiramer acetate in patients with uveitis associated to MS could be effective to reduce uveitis episodes, and has been well tolerated by the majority of patients. Future studies with higher numbers of cases are necessary to confirm these promising results.Conflict of interestsNo conflict of interests was declared by the authors in relation to the present study. The authors declare that they have not received grants or funding of any type in relation to the preparation of the study. The authors state that they are exclusively responsible for the contents and preparation of this article. The authors declare that they do not have commercial interests and have not received financial support for the preparation of this study." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres845217" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Aim" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec840099" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres845216" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec840098" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and methods" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Results" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Clinic characteristics of multiple sclerosis" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Complications" ] ] ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflict of interests" ] 9 => array:2 [ "identificador" => "xack283961" "titulo" => "Acknowledgments" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-09-14" "fechaAceptado" => "2016-11-29" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec840099" "palabras" => array:5 [ 0 => "Interferon-β" 1 => "Glatiramer acetate" 2 => "Multiple sclerosis-associated uveitis" 3 => "Multiple sclerosis" 4 => "Uveitis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec840098" "palabras" => array:5 [ 0 => "Interferón-β" 1 => "Acetato de glatirámero" 2 => "Uveítis asociada a esclerosis múltiple" 3 => "Esclerosis múltiple" 4 => "Uveítis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "AimTo analyze the role of interferon-β or glatiramer acetate in reducing the inflammatory episodes of intra-ocular inflammation in multiple sclerosis-associated uveitis. MethodA study was conducted on a non-randomized, retrospective case series of 13 patients with proven multiple sclerosis and uveitis (minimum follow-up, 12 months). All patients were given immunomodulatory treatment (interferon-β or glatiramer acetate) to control the course of the multiple sclerosis. Patients were compared to themselves before initiating the treatment, in order to assess the difference in uveitis episodes. The main outcome measurements were the number of uveitis episodes with/without immunomodulatory treatment. ResultsUveitis was bilateral in 10 (77%) out of 13 patients. Intermediate uveitis was observed in 11 patients, retinal vasculitis in 3 patients, and one patient was classified as a posterior uveitis. The patients had a mean of 4.15±3.1 episodes of uveitis (range 1–10) during the follow-up period (148.6±84.3 months). When compared to their pre-treatment status, patients on treatment with interferon-β or glatiramer acetate showed a significant decrease of 0.36 episodes of ocular inflammation per year (p=0.02). Mild side effects related to immunomodulatory treatment were observed in 6 (46%) patients, 3 (23%) patients with a flu-like syndrome, and 3 (23%) patients with a skin rash. ConclusionsInterferon β or glatiramer acetate could be effective in reducing the uveitis episodes in patients with multiple sclerosis-associated uveitis, and was well tolerated in most patients." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Aim" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoAnalizar la eficacia del interferón-β o acetato de glatirámero en reducir los episodios de inflamación intraocular en pacientes con uveítis asociada a esclerosis múltiple. MétodoEstudio no aleatorizado, retrospectivo de serie de casos de 13 pacientes con diagnóstico definitivo de esclerosis múltiple y uveítis (seguimiento mínimo, 12 meses). Todos los pacientes fueron tratados con terapia inmunomoduladora (interferón-β o acetato de glatirámero) para controlar el curso de la esclerosis múltiple. Los pacientes fueron comparados con ellos mismos antes de iniciar el tratamiento inmunomodulador para valorar la diferencia en los episodios de uveítis. Variable principal de medida: número de episodios de uveítis con/sin tratamiento inmunomodulador. ResultadosLos brotes de uveítis fueron bilaterales en 10 de 13 pacientes (77%). Once pacientes fueron clasificados como uveítis intermedias, 3 pacientes como vasculitis retiniana y un paciente como uveítis posterior. Los pacientes tuvieron una media de 4,15±3,1 episodios de uveítis (rango 1-10) a lo largo del seguimiento (148,6±84,3 meses). Los pacientes bajo tratamiento con interferón-β o acetato de glatirámero mostraron una reducción significativa de 0,36 episodios de inflamación intraocular al año (p=0,02) comparados con ellos mismos antes de iniciar el tratamiento. Seis pacientes (46%) mostraron efectos secundarios leves asociados al tratamiento inmunomodulador (3 pacientes [23%] síndrome seudogripal; 3 pacientes [23%] rash cutáneo). ConclusionesEl interferón-β o acetato de glatirámero podrían ser efectivos en reducir los brotes de inflamación intraocular en pacientes con uveítis asociada a esclerosis múltiple, siendo bien tolerados por la mayoría de los pacientes." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Velazquez-Villoria D, Macia-Badia C, Segura-García A, Pastor Idoate S, Arcos-Algaba G, Velez-Escola L, et al. Eficacia del tratamiento inmunomodulador con interferón-β o acetato de glatirámero en las uveítis asociadas a esclerosis múltiple. Arch Soc Esp Oftalmol. 2017;92:273–279." ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "MS: multiple sclerosis; F: female; M: male; RR: recurring-remitting forms of MS; SP: secondarily progressive forms of MS; UI: intermediate uveitis; Ret Vasc: retinal vasculitis." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Sex \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Age at uveitis diagnostic (years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Uveitis type \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Overall number of uveitis episodes \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Age at MS diagnostic (years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">MS course (at the end of follow-up) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Follow-up (months) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">UI+Vasc Ret \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">336 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">UI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">UI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">144 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Posterior \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">UI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">144 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">UI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">90 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ret Vasc \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">UI+Ret Vasc \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">144 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">UI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">UI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">UI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">UI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">UI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">252 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1427464.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinic characteristics of patients with uveitis associated to multiple sclerosis." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Glatiramer: glatiramer acetate; IFN-β: interferon-β; IM-T: immunomodulator treatment." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"># of uveitis episodes before IM-T \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Follow-up before IM-T (years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"># of uveitis episodes/years follow-up without IM-T \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">IM-T \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"># of uveitis episodes during IM-T \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Duration de IM-T (years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"># of uveitis episodes/years follow-up without IM-T \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Side effects efectos secundarios \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.417 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IFNβ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.667 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IFNβ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.174 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Glatiramer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.142 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IFNβ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.889 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.909 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IFNβ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rash \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.462 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IFNβ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.428 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IFNβ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Flu-like syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.625 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IFNβ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IFNβ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.434 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.667 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IFNβ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Flu-like syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.434 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Glatiramer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rash \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Glatiramer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Flu-like syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.299 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IFNβ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.465 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rash \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1427465.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Effects of immunomodulatory treatment on the number of uveitis episodes in patients with uveitis associated to MS. 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Original article

Efficacy of immunomodulatory therapy with interferon-β or glatiramer acetate on multiple sclerosis-associated uveitis

Eficacia del tratamiento inmunomodulador con interferón-β o acetato de glatirámero en las uveítis asociadas a esclerosis múltiple

D. Velazquez-Villoriaa,

Corresponding author

dvvilloria@gmail.com

Corresponding author.

, C. Macia-Badiaa, A. Segura-Garcíaa, S. Pastor Idoatea, G. Arcos-Algabaa, L. Velez-Escolaa, J. García-Arumía,b

a Servicio de Oftalmología, Hospital Vall de Hebron, Barcelona, Spain

b Departamento de Oftlamología, Instituto de Microcirugía Ocular, Barcelona, Spain

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        "titulo" => "Eficacia del tratamiento inmunomodulador con interfer&#243;n-&#946; o acetato de glatir&#225;mero en las uve&#237;tis asociadas a esclerosis m&#250;ltiple"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Multiple sclerosis &#40;MS&#41; is a chronic and presumably self immune demyelinizing inflammatory disease of the central nervous system&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> Association of MS and uveitis is infrequent and occurs in 0&#46;65&#8211;10&#37; of Caucasian patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">2&#44;3</span></a> Ocular involvement could be the initial expression of the disease in some patients&#46; Optic neuritis is the most frequent ocular expression of MS&#44; with an incidence approaching 30&#37; of these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">2</span></a> Foveal inflammation is significantly less frequent&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">It has been demonstrated that patients with MS exhibit higher risk of developing uveitis&#44; probably due to sharing target antigens&#44; genetic susceptibilities or alterations in immunological homeostasis&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">2&#44;3</span></a> Approximately 1&#37; of patients with MS develop uveitis episodes in the course of the disease&#44; and 1&#37; of patients with uveitis associate MS&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> This association between uveitis and MS indicates that both entities share etiopathogenic mechanisms and therefore both could respond to the same treatment&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Uveitis episodes usually respond to locally or systemically administrated corticoids&#46; Interferon-&#946; &#40;IFN&#946;&#41; or glatiramer acetate are immunomodulator agents that efficiently diminish the frequency and severity of MS episodes as well as the progression of the disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">4&#8211;9</span></a> In addition&#44; treating uveitis episodes associated to MS with IFN&#946; seems to have a beneficial effect as regards visual acuity and intraocular inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> To date&#44; there is no clear evidence about the efficacy of any medication capable of reducing the number of uveitis episodes in patients with MS&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The main objective of the present study is to analyze the role of immunomodulator therapy with IFN&#946; or glatiramer acetate in the reduction of the number of intraocular inflammation episodes in patients with uveitis associated to MS&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">A retrospective&#44; non-controlled study of patients with uveitis and MS diagnostic that received immunomodulator treatment included in the database of the Ophthalmology and Neuroimmunology Dept&#46; of the Vall d&#8217;Hebron hospital of Barcelona between 1990 and 2013&#46; The study was approved by the ethics committee of the authors&#8217; institution in accordance with the guidelines of the Helsinki declaration and good clinical practices&#46; All patients read and signed an informed consent document&#44; authorizing the use of the information in their medical records for the present study&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The MS diagnostic was established by the specialist of the Neuroimmunology Dept&#46; on the basis of a neurologic examination and magnetic resonance findings&#44; in accordance with the revised McDonald criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">11</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The study included patients with a definitive MS diagnostic and were treated with IFN&#946; or glatiramer acetate prescribed by the specialist of the Neuroimmunology Dept&#46; for controlling the course of MS and who also exhibited clinically significant intraocular inflammation episodes&#46; In addition&#44; all the patients were examined by an internist physician and carried out the appropriate diagnostic studies to discard the possibility of other related systemic diseases&#46; The study excluded the patients with self immune diseases that could be related to uveitis&#44; patients with less than 12 months follow-up or with incomplete clinical records&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The classification of uveitis was based on the criteria of the <span class="elsevierStyleItalic">International Uveitis Study Group</span> &#40;IUSG&#41;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a> as regards the anatomic location &#40;anterior&#44; intermediate&#44; posterior or panuveitis&#41;&#46; A new outbreak of intraocular inflammatory activity was regarded as an increase in 2 or more cellularity levels in the anterior chamber or vitreous cavity&#44; applying the criteria of the <span class="elsevierStyleItalic">SUN Working Group</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a> associated to diminished vision or increased myodesopsia&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The anterior uveitis episodes were treated with topical corticoids &#40;dexamethasone 1<span class="elsevierStyleHsp" style=""></span>mg&#47;ml&#44; eyedrops&#41; and midriatics &#40;1&#37; cyclopentolate eyedrops&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The intermediate and posterior uveitis episodes were treated with systemic corticoids &#40;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg prednisone&#41; in cases exhibiting bilateral involvement&#44; or with subtenon or intraocular corticoid injections &#40;1<span class="elsevierStyleHsp" style=""></span>mg&#47;ml triamcinolone acetonid&#41; in cases with unilateral involvement or cystic macular edema&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Sector photocoagulation with argon laser was applied in occlusive vasculitis with marked retinal ischemia evidenced in fluorescein angiography&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">All patients received immunomodulator treatment &#40;IFN&#946; or glatiramer acetate&#41; prescribed for controlling MS by Neuroimmunology Dept&#46; specialists&#46; Immunomodulator treatment was not prescribed in any case for controlling uveitis episodes&#46; Patients treated with IFN&#946;1a were given a weekly intramuscular dose of 30<span class="elsevierStyleHsp" style=""></span>&#956;g &#40;Avonex<span class="elsevierStyleSup">&#174;</span>&#44; Biogen Inc&#46;&#44; Cambridge&#44; Massachusetts&#44; USA&#41;&#46; Patients treated with glatiramer acetate were given daily subcutaneous 20<span class="elsevierStyleHsp" style=""></span>mg injections&#46; The type of medication was based on the criteria of neurologists for controlling the course of MS&#46; The degree of disability associated to MS was assessed according to the <span class="elsevierStyleItalic">Expanded Disability Status Score</span> &#40;EDSS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">14</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The statistical analysis was developed with the SPSS for Windows&#44; version 17&#46;0 &#40;SPSS&#44; Chicago&#44; IL&#44; USA&#41;&#46; The Wilcoxon test for paired data was applied for comparing the number of uveitis episodes exhibited by patients during the immunomodulator treatment vs without immunomodulator treatment&#46; Taking into account that the follow-up period is different before vs during immunomodulator treatment&#44; the measurement scale was unified in order to make said periods comparable&#58; calculating the mean number of uveitis episodes&#47;years of follow-up &#40;before and during the immunomodulator treatment&#41;&#46; A value of p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was taken as statistically significant&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">Overall&#44; 16 patients with uveitis episodes associated to MS in treatment with immunomodulator medicaments were initially included in the study&#46; However&#44; 3 were excluded &#40;2 patients with less than 12 months follow-up and one due to incomplete medical records&#41;&#46; Taking into account the above inclusion and exclusion criteria&#44; the results of 13 patients &#40;7 females and 6 males&#41; were analyzed after a mean follow-up of 148&#46;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>84&#46;30 months &#40;range&#44; 12&#8211;252 months&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Mean age at uveitis episodes diagnostic was 39&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;5 years &#40;range&#44; 21&#8211;57 years&#41;&#59; and presentation of neurological symptoms of 35&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;5 years &#40;range&#44; 21&#8211;49 years&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Neurological symptoms preceded uveitis in 9 of the 13 patients &#40;69&#46;2&#37;&#41; with a mean time period of 114 months &#40;range&#44; 32&#8211;216 months&#41;&#59; whereas in the remaining 4 patients uveitis appeared before neurological symptoms in a mean time period of 86 months &#40;range&#44; 20&#8211;216 months&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Uveitis episodes were bilateral in 10 of 13 patients &#40;77&#37;&#41;&#46; Patients had a mean of 4&#46;15 intraocular inflammation episodes &#40;range&#44; 1&#8211;10 episodes&#41; throughout the follow-up period&#46; In 11 patients &#40;84&#46;6&#37;&#41; the predominant clinic form was intermediate uveitis&#44; with 6 associating significant anterior inflammation&#46; Three patients exhibited occlusive retinal vasculitis and a further case had posterior uveitis&#46; This unique case was classified as a multifocal posterior retinochoroiditis&#46; Ocular fundus examination revealed multiple cream-colored retinochoroidal lesions in the posterior pole of both eyes&#44; with exudation in the early and intermediate phase of fluorescein angiography&#46; A range of analytical and imaging tests &#40;thorax x-ray and CAT&#41; were made on this patient to discard a sarcoidosis diagnostic&#46; In this unique patient&#44; MS had been diagnosed 18 years prior to the onset of retinochoroidal lesions and exhibited a secondarily progressive form of MS&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Medical treatment for controlling intraocular inflammation required oral prednisone for all patients&#46; It became necessary to associate an immunosuppressant &#40;cyclosporine&#41; for 2 patients who were not taking immunomodulatory treatment at the time&#46; When subsequently said patients initiated treatment with immunomodulator medicaments for controlling the course of MS&#44; the intraocular inflammation episodes resolved without having to utilize cyclosporine&#46; In 5 eyes of 3 patients&#44; the presence of cystic macular edema was identified and treated with periocular triamcinolone injections&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Occlusive vasculitis episodes were detected in 4 eyes of 3 patients &#40;23&#37;&#41;&#44; who developed neovascularization in the retina and one in the optic disk&#46; They were all successfully treated with sector argon laser photocoagulation of the compromised area&#46; None of the patients developed iris neovascularization or neovascular glaucoma&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Clinic characteristics of multiple sclerosis</span><p id="par0100" class="elsevierStylePara elsevierViewall">The course of MS was recurrent-remitting in 11 patients &#40;88&#46;9&#37;&#41; and secondarily progressive in 2 patients &#40;11&#46;1&#37;&#41;&#46; Only one patient exhibited a secondarily progressive form of MS when uveitis was diagnosed&#46; The clinic characteristics of the 13 patients are shown in detail in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">The mean disability value as per EDSS at the last visit was globally 3&#46;8 for the series&#46; The patients who exhibited neurological symptoms prior to uveitis had a higher mean EDSS score in the last visit &#40;mean 4&#46;53&#59; mean follow-up&#44; 176&#46;6 months&#41; compared to those who exhibited uveitis prior to neurological symptoms &#40;mean 2&#46;62&#59; mean follow-up&#44; 120 months&#41;&#44; although the difference was not statistically significant &#40;<span class="elsevierStyleItalic">U</span> Mann&#8211;Whitney test&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;306&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Ten patients received immunomodulator treatment with IFN&#946; &#40;mean treatment duration&#58; 41&#46;5 months&#41; and 3 patients were treated with glatiramer acetate &#40;mean treatment duration&#58; 11&#46;3 months&#41;&#44; according to the criteria of neuroimmunology specialists for controlling the evolution of MS&#46; None of the patients exhibited active uveitis when beginning immunomodulator therapy&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">A statistically significant reduction of the mean number of uveitis episodes&#47;follow-up years during treatment with immunomodulator medicaments &#40;IFN&#946; or glatiramer acetate&#41; was evidenced&#46; The achieved reduction was 0&#46;36 uveitis episodes&#47;year&#44; compared to the period of time during which patients did not receive immunomodulator treatment &#40;Wilcoxon test for paired data&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows a detailed description of immunomodulator therapy and uveitis episodes&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Complications</span><p id="par0120" class="elsevierStylePara elsevierViewall">Six out of 13 patients &#40;46&#37;&#41; in treatment with immunomodulator therapy exhibited side effects related to IFN&#946; or glatiramer acetate&#44; consisting in flu-like symptoms in 3 patients &#40;23&#37;&#41; and skin rash in 3 patients &#40;23&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Immunomodulator treatment was not discontinued in any case&#44; following the criteria of the Neuroimmunology Dept&#46; specialists&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0125" class="elsevierStylePara elsevierViewall">The present study collected the data of 13 patients with a confirmed diagnostic of MS and intraocular inflammation episodes&#46; Even though several studies described said association&#44; there are few series with higher amounts of patients published in the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">2&#44;10</span></a> Demographic and chronological data of the series match those of other published series<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">9&#44;11</span></a> with the association between MS and uveitis being characteristic in young females with recurring-remitting forms of MS&#46; The predominance of the females in this association varies between 60&#37;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">2</span></a> and 82&#37;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">15</span></a> in different series&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">In some studies&#44; the appearance of neurological symptoms can precede intraocular inflammation &#40;up to 60&#37; of cases in some series<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a>&#41;&#44; whereas in other studies uveitis episodes preceded neurological symptoms up to several years&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">16</span></a> Even though the majority of patients in the present series had MS diagnosed when uveitis expressed&#44; 4 patients &#40;30&#46;7&#37;&#41; first had intraocular inflammation episodes&#44; with a considerable time interval before the onset of neurological symptoms&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">A recently published study<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">17</span></a> indicates that the concomitant presence of uveitis in patients with MS could be a positive prognostic factor for the severity of MS&#46; In accordance with said study&#44; the majority of the present study patients developed recurring-remitting forms of MS&#46; In contrast with other published series&#44;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">10&#44;16&#44;18</span></a> the patients of this series who had uveitis before neurological symptoms demonstrated better prognosis in what concerns final neurological disability measured in the EDSS scale when compared to those whose neurological symptoms expressed before uveitis&#44; although this difference was not statistically significant and could be attributed to the limited number of patients included in the series&#46; These findings should be confirmed in future studies with higher numbers of cases&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The effectiveness of IFN&#946; in patients with MS<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">4&#44;5</span></a> and&#47;or optic neuritis has been demonstrated&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> Jacobs et al&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">6</span></a> demonstrated that beginning treatment with IFN at the first demyelinizing event such as optic neuritis is beneficial for patients with cerebral lesions shown in magnetic resonance that indicate a high risk of clinically definitive MS&#46; The efficacy of this therapy has been confirmed in subsequent clinic trials&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">7&#44;8</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">In the experimental allergic encephalomyelitis animal model&#44; a classic MS model in experimentation animals&#44; it was demonstrated that animals could also develop bilateral uveitis episodes&#44;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">19</span></a> and that treatment with IFN&#946;1 diminished intraocular inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">20</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">In clinic trials&#44; glatiramer acetate has demonstrated its efficacy in patients with recurring-remitting forms of MS diminishing recurrence rates and demyelinizing activity assisted by magnetic resonance&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">There are no previous studies assessing the effect of immunomodulator therapy &#40;IFN&#946; or glatiramer acetate&#41; in what concerns the number of intraocular inflammation episodes in uveitis associated to MS&#46; Becker et al&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> demonstrated a beneficial effect of IFN in 13 patients with uveitis associated to MS&#44; in terms of visual acuity improvement and intraocular inflammation activity&#46; However they did not to research whether said therapy could diminish the number of uveitis episodes&#46; The authors have not found other series in the literature referring to the effect of glatiramer acetate in uveitis associated to MS&#44; the present paper being the first in this regard&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The results of the present study demonstrate a statistically significant reduction in the number of intraocular inflammation episodes in patients being treated with IFN&#946; or glatiramer acetate&#44; compared to the same patients before immunomodulator treatment&#46; This seems to indicate the existence of shared antigen factors between neurological and ophthalmological expressions of the uveitis-MS range with similar pathogenic mechanisms&#46; This beneficial effect could be particularly interesting for patients with partial resistance to systemic corticoids or immunosuppressant medicaments&#46; The majority of patients did not exhibit relevant side effects attributed to immunomodulator therapy and those which did appear were well tolerated in the majority of cases&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Intermediate uveitis was the most common expression in the present series&#44; in accordance with the findings of the majority of uveitis and MS series&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">13&#8211;15</span></a> However&#44; in other studies the posterior or anterior uveitis forms appear with greater frequency&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">2&#44;16</span></a> These differences could be partly due to the different interpretation of the IUSG uveitis classification criteria<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a> because&#44; even though intraocular inflammation predominates at the pars plana level in the majority of cases&#44; it could sometimes extend toward the iris and the anterior chamber&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">14</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The results of the present study demonstrate that corticoid therapy enables adequate control of intraocular inflammation episodes associated to MS in the majority of cases&#44; requiring immunosuppressant agents only in isolated cases resistant to corticoid treatment &#40;only 2 in the present series&#41;&#46; Immunomodulator therapy was not prescribed in any case for controlling uveitis episodes&#44; as the intraocular inflammation outbreaks were adequately controlled with corticoid therapy&#46; Accordingly&#44; it was not possible to assess the effect of immunomodulator therapy on the inflammatory activity in the anterior chamber&#44; vitreous cavity&#44; macular edema or retinal vasculitis&#46; Due to the small sample size it was not possible to carry out the comparative study of the efficacy of treatment with IFN&#946; against glatiramer acetate in the reduction of uveitis episodes&#46; Taking into account the findings of Becker et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> treatment with IFN&#946; should be considered in unique uveitis cases that are resistant to corticoid therapy&#46; In their study&#44; Becker et al&#46; treated 13 patients with uveitis and MS refractory to steroid treatment with IFN&#44; obtaining visual acuity improvements in 71&#37; of patients and avoiding the use of steroid therapy in 69 of patients after 2 years of treatment with IFN&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> However&#44; it is also necessary to consider the recent study by Jouve et al&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a> that shows that the use of IFN for controlling MS in patients with concomitant uveitis could be associated to poor evolution of uveitis&#46; In said study&#44; patients with uveitis and MS treated with IFN developed higher percentages of chronic uveitis&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a> The limited number of patients in both studies&#44; as well as its retrospective nature&#44; do not enable definitive conclusions about the matter&#46; Additional prospective studies are necessary with higher numbers of patients to obtain further evidence about the efficacy of treating patients with uveitis associated to MS with IFN&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The limitations of the present study include its retrospective design&#44; the limited number of cases and the fact that spontaneous inflammatory activity improvements might not have been recognized&#46; Considering that MS can exhibit a recurring-remitting course and that uveitis can sometimes follow the pattern of the underlying MS&#44; patients might have improved regardless of the treatment they were receiving&#46; In addition&#44; caution is advised when interpreting the present results because&#44; by studying a limited number of cases and a different follow-up period before and during immunomodulator treatment&#44; small changes in the number of intraocular inflammation episodes could have repercussions for statistical significance&#46; For this reason&#44; even though this study found a statistically significant reduction in the mean of uveitis episodes per follow-up year during immunomodulator treatment&#44; this finding has only exploratory value and should be confirmed by series with higher numbers of cases and longer follow-up periods&#46; The present series has studied the effect of immunomodulatory treatments on the number of uveitis episodes associated to MS&#46; The design of the study does not allow an assessment of the effects of immunomodulator therapy on inflammatory activity in the anterior chamber&#44; vitreous cavity&#44; macular edema or retinal vasculitis&#46; It would be of interest to carry out a prospective study with more patients to assess the efficacy of immunomodulatory treatments on intraocular inflammatory activity as well as to compare the differences or similarities between both immunomodulator treatments&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">In conclusion&#44; treatment with IFN&#946; or glatiramer acetate in patients with uveitis associated to MS could be effective to reduce uveitis episodes&#44; and has been well tolerated by the majority of patients&#46; Future studies with higher numbers of cases are necessary to confirm these promising results&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflict of interests</span><p id="par0185" class="elsevierStylePara elsevierViewall">No conflict of interests was declared by the authors in relation to the present study&#46; The authors declare that they have not received grants or funding of any type in relation to the preparation of the study&#46; The authors state that they are exclusively responsible for the contents and preparation of this article&#46; The authors declare that they do not have commercial interests and have not received financial support for the preparation of this study&#46;</p></span></span>"
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          "identificador" => "xres845216"
          "titulo" => "Resumen"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Objetivo"
            ]
            1 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "M&#233;todo"
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            2 => array:2 [
              "identificador" => "abst0035"
              "titulo" => "Resultados"
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            3 => array:2 [
              "identificador" => "abst0040"
              "titulo" => "Conclusiones"
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        ]
        3 => array:2 [
          "identificador" => "xpalclavsec840098"
          "titulo" => "Palabras clave"
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        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Material and methods"
        ]
        6 => array:3 [
          "identificador" => "sec0015"
          "titulo" => "Results"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Clinic characteristics of multiple sclerosis"
            ]
            1 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Complications"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Conflict of interests"
        ]
        9 => array:2 [
          "identificador" => "xack283961"
          "titulo" => "Acknowledgments"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2016-09-14"
    "fechaAceptado" => "2016-11-29"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec840099"
          "palabras" => array:5 [
            0 => "Interferon-&#946;"
            1 => "Glatiramer acetate"
            2 => "Multiple sclerosis-associated uveitis"
            3 => "Multiple sclerosis"
            4 => "Uveitis"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec840098"
          "palabras" => array:5 [
            0 => "Interfer&#243;n-&#946;"
            1 => "Acetato de glatir&#225;mero"
            2 => "Uve&#237;tis asociada a esclerosis m&#250;ltiple"
            3 => "Esclerosis m&#250;ltiple"
            4 => "Uve&#237;tis"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Aim</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To analyze the role of interferon-&#946; or glatiramer acetate in reducing the inflammatory episodes of intra-ocular inflammation in multiple sclerosis-associated uveitis&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A study was conducted on a non-randomized&#44; retrospective case series of 13 patients with proven multiple sclerosis and uveitis &#40;minimum follow-up&#44; 12 months&#41;&#46; All patients were given immunomodulatory treatment &#40;interferon-&#946; or glatiramer acetate&#41; to control the course of the multiple sclerosis&#46; Patients were compared to themselves before initiating the treatment&#44; in order to assess the difference in uveitis episodes&#46; The main outcome measurements were the number of uveitis episodes with&#47;without immunomodulatory treatment&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Uveitis was bilateral in 10 &#40;77&#37;&#41; out of 13 patients&#46; Intermediate uveitis was observed in 11 patients&#44; retinal vasculitis in 3 patients&#44; and one patient was classified as a posterior uveitis&#46; The patients had a mean of 4&#46;15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;1 episodes of uveitis &#40;range 1&#8211;10&#41; during the follow-up period &#40;148&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>84&#46;3 months&#41;&#46; When compared to their pre-treatment status&#44; patients on treatment with interferon-&#946; or glatiramer acetate showed a significant decrease of 0&#46;36 episodes of ocular inflammation per year &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46; Mild side effects related to immunomodulatory treatment were observed in 6 &#40;46&#37;&#41; patients&#44; 3 &#40;23&#37;&#41; patients with a flu-like syndrome&#44; and 3 &#40;23&#37;&#41; patients with a skin rash&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Interferon &#946; or glatiramer acetate could be effective in reducing the uveitis episodes in patients with multiple sclerosis-associated uveitis&#44; and was well tolerated in most patients&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Aim"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Method"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Analizar la eficacia del interfer&#243;n-&#946; o acetato de glatir&#225;mero en reducir los episodios de inflamaci&#243;n intraocular en pacientes con uve&#237;tis asociada a esclerosis m&#250;ltiple&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio no aleatorizado&#44; retrospectivo de serie de casos de 13 pacientes con diagn&#243;stico definitivo de esclerosis m&#250;ltiple y uve&#237;tis &#40;seguimiento m&#237;nimo&#44; 12 meses&#41;&#46; Todos los pacientes fueron tratados con terapia inmunomoduladora &#40;interfer&#243;n-&#946; o acetato de glatir&#225;mero&#41; para controlar el curso de la esclerosis m&#250;ltiple&#46; Los pacientes fueron comparados con ellos mismos antes de iniciar el tratamiento inmunomodulador para valorar la diferencia en los episodios de uve&#237;tis&#46; Variable principal de medida&#58; n&#250;mero de episodios de uve&#237;tis con&#47;sin tratamiento inmunomodulador&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Los brotes de uve&#237;tis fueron bilaterales en 10 de 13 pacientes &#40;77&#37;&#41;&#46; Once pacientes fueron clasificados como uve&#237;tis intermedias&#44; 3 pacientes como vasculitis retiniana y un paciente como uve&#237;tis posterior&#46; Los pacientes tuvieron una media de 4&#44;15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#44;1 episodios de uve&#237;tis &#40;rango 1-10&#41; a lo largo del seguimiento &#40;148&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>84&#44;3 meses&#41;&#46; Los pacientes bajo tratamiento con interfer&#243;n-&#946; o acetato de glatir&#225;mero mostraron una reducci&#243;n significativa de 0&#44;36 episodios de inflamaci&#243;n intraocular al a&#241;o &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;02&#41; comparados con ellos mismos antes de iniciar el tratamiento&#46; Seis pacientes &#40;46&#37;&#41; mostraron efectos secundarios leves asociados al tratamiento inmunomodulador &#40;3 pacientes &#91;23&#37;&#93; s&#237;ndrome seudogripal&#59; 3 pacientes &#91;23&#37;&#93; rash cut&#225;neo&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El interfer&#243;n-&#946; o acetato de glatir&#225;mero podr&#237;an ser efectivos en reducir los brotes de inflamaci&#243;n intraocular en pacientes con uve&#237;tis asociada a esclerosis m&#250;ltiple&#44; siendo bien tolerados por la mayor&#237;a de los pacientes&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todo"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Velazquez-Villoria D&#44; Macia-Badia C&#44; Segura-Garc&#237;a A&#44; Pastor Idoate S&#44; Arcos-Algaba G&#44; Velez-Escola L&#44; et al&#46; Eficacia del tratamiento inmunomodulador con interfer&#243;n-&#946; o acetato de glatir&#225;mero en las uve&#237;tis asociadas a esclerosis m&#250;ltiple&#46; Arch Soc Esp Oftalmol&#46; 2017&#59;92&#58;273&#8211;279&#46;</p>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">MS&#58; multiple sclerosis&#59; F&#58; female&#59; M&#58; male&#59; RR&#58; recurring-remitting forms of MS&#59; SP&#58; secondarily progressive forms of MS&#59; UI&#58; intermediate uveitis&#59; Ret Vasc&#58; retinal vasculitis&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Age at uveitis diagnostic &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Uveitis type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Overall number of uveitis episodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Age at MS diagnostic &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">MS course &#40;at the end of follow-up&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Follow-up &#40;months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">UI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Vasc Ret&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">336&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">UI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">UI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">144&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Posterior&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">UI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">144&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">UI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ret Vasc&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">UI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Ret Vasc&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">144&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">UI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">UI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">UI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">UI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">UI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">252&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Glatiramer&#58; glatiramer acetate&#59; IFN-&#946;&#58; interferon-&#946;&#59; IM-T&#58; immunomodulator treatment&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">&#35; of uveitis episodes before IM-T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Follow-up before IM-T &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">&#35; of uveitis episodes&#47;years follow-up without IM-T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">IM-T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">&#35; of uveitis episodes during IM-T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Duration de IM-T &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">&#35; of uveitis episodes&#47;years follow-up without IM-T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Side effects efectos secundarios&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;417&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFN&#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;667&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFN&#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;174&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Glatiramer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;142&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFN&#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;889&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;909&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFN&#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rash&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;462&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFN&#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;428&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFN&#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Flu-like syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;625&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFN&#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFN&#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;434&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;667&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFN&#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Flu-like syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;434&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Glatiramer&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rash&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Flu-like syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;299&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFN&#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;465&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rash&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Effects of immunomodulatory treatment on the number of uveitis episodes in patients with uveitis associated to MS&#46; Comparison of the number of intraocular inflammation episodes before and after immunomodulatory treatment&#46;</p>"
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      ]
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